Aging & Metabolism Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Chapman S212, Oklahoma City, OK, 73104, USA.
Faculdade de Veterinária, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
Geroscience. 2023 Aug;45(4):2109-2120. doi: 10.1007/s11357-022-00601-8. Epub 2022 Jun 11.
17α-estradiol (17α-E2) is referred to as a nonfeminizing estrogen that was recently found to extend healthspan and lifespan in male, but not female, mice. Despite an abundance of data indicating that 17α-E2 attenuates several hallmarks of aging in male rodents, very little is known with regard to its effects on feminization and fertility. In these studies, we evaluated the effects of 17α-E2 on several markers of male reproductive health in two independent cohorts of mice. In alignment with our previous reports, chronic 17α-E2 treatment prevented gains in body mass, but did not adversely affect testes mass or seminiferous tubule morphology. We subsequently determined that chronic 17α-E2 treatment also did not alter plasma 17β-estradiol or estrone concentrations, while mildly increasing plasma testosterone levels. We also determined that chronic 17α-E2 treatment did not alter plasma follicle-stimulating hormone or luteinizing hormone concentrations, which suggests 17α-E2 treatment does not alter gonadotropin-releasing hormone neuronal function. Sperm quantity, morphology, membrane integrity, and various motility measures were also unaffected by chronic 17α-E2 treatment in our studies. Lastly, two different approaches were used to evaluate male fertility in these studies. We found that chronic 17α-E2 treatment did not diminish the ability of male mice to impregnate female mice, or to generate successfully implanted embryos in the uterus. We conclude that chronic treatment with 17α-E2 at the dose most commonly employed in aging research does not adversely affect reproductive fitness in male mice, which suggests 17α-E2 does not extend lifespan or curtail disease parameters through tradeoff effects with reproduction.
17α-雌二醇（17α-E2）被称为非雌性化雌激素，最近发现它可以延长雄性而不是雌性小鼠的健康寿命和寿命。尽管有大量数据表明 17α-E2 可以减轻雄性啮齿动物的几种衰老特征，但对于它对雌性化和生育能力的影响却知之甚少。在这些研究中，我们评估了 17α-E2 在两个独立的小鼠队列中对几种雄性生殖健康标志物的影响。与我们之前的报告一致，慢性 17α-E2 治疗可防止体重增加，但不会对睾丸质量或生精小管形态产生不利影响。随后我们确定，慢性 17α-E2 治疗也不会改变血浆 17β-雌二醇或雌酮浓度，而轻度增加血浆睾酮水平。我们还确定，慢性 17α-E2 治疗不会改变血浆促卵泡激素或黄体生成素浓度，这表明 17α-E2 治疗不会改变促性腺激素释放激素神经元功能。在我们的研究中，慢性 17α-E2 治疗也不会改变精子数量、形态、膜完整性和各种运动措施。最后，我们使用两种不同的方法来评估这些研究中的雄性生育能力。我们发现，慢性 17α-E2 治疗不会降低雄性小鼠使雌性小鼠受孕的能力，也不会降低其在子宫中成功植入胚胎的能力。我们得出结论，在最常用于衰老研究的剂量下，慢性 17α-E2 治疗不会对雄性小鼠的生殖适应性产生不利影响，这表明 17α-E2 不会通过与生殖的权衡效应来延长寿命或缩短疾病参数。
